LIVER IMMUNOLOGY : principles and practice.

• Publisher: SPRINGER
• Year: 2020
• Tongue: English
• Leaves: 631
• Edition: 3
• Category: Library

✦ Table of Contents

Preface
Contents
Contributors
1: Core Concepts in Immunology: The Definition of Autoimmunity and Its Unique Application to the Seat of Tolerance, the Liver
Danger Signal Recognition by Innate Immune Cells
Adaptive Immunity
Antigen Recognition by T-Cell Receptors
T-Cell Activation
Effector Functions of the Adaptive Immune System and Their Regulation
B-Cell Antigen Receptors (Antibodies)
Local and Systemic Inflammation
Regulation of Inflammation
Liver Anatomy and Microanatomy
Liver Immune Tolerance
The Unique Characteristics of Hepatic Immune Cells and Their Role in Supporting Immune Tolerance
The Influence of Hepatic Exposure to Gut-Derived Products on Liver Tolerance
The Definition of Autoimmunity and Loss of Immune Tolerance
Autoimmunity in a Tolerogenic Organ, the Liver
References
2: The Liver as a Lymphoid Organ
Introduction
Liver Anatomy and Cell Composition
Predominance of Innate Immunity in Liver
Antigen-Presenting Cells
Hepatocytes
LSECs
BECs
KCs and Bone Marrow-Derived Macrophages
DCs
HSCs
Innate Lymphocytes
NKT Cells
MAIT Cells
NK Cells/Liver-Resident NK Cells
Innate Lymphoid Cells (ILCs)
γδ T Cells
Adaptive Immune Cells
T/B Cells
Tissue-Resident Memory T (Trm) Cells
Liver as a Tolerogenic Organ: Mechanisms
Regulation of the Immune Response by the Liver Microenvironment
Extracellular Matrix (ECM) Regulation of Immune Cell Response in the Liver
Bile Acid Regulation of Immune Response in the Liver
Metabolic Regulation of Liver Immune Response
Hematopoiesis in the Liver
Summary
References
3: The Uniqueness of Innate Immunity
Introduction
Overview of Innate Immune Cell Types in the Liver
Monocytes and Macrophages
Kupffer Cells
Granulocytes: Neutrophils, Basophils, and Eosinophils
Dendritic Cells
NK Cells and NKT Cells
Pattern Recognition Receptors
PAMPs and DAMPs
Toll-Like Receptors
Helicase Receptors
NLRs and Inflammasomes
Cytokines and Chemokines
Proinflammatory Cytokines and Chemokines
Anti-inflammatory Cytokines
Regulatory Mediators
Role of Innate Immunity in Liver Diseases
Gut–Liver Axis
Alcoholic Liver Disease
NAFLD and NASH
PBC and PSC
Viral Hepatitis
HCC
Summary
References
4: Adaptive Immunity and the Clinical Definition of Autoantibodies
Activation of Adaptive Immunity
T-Cell Activation
B-Cell Activation
Autoimmunity and Autoantibodies
Laboratory Methods to Detect Autoantibodies
Anti-Nuclear Antibody
History
Methods of Detection, Immunofluorescence Reactivities, and Antigenic Targets
Clinical Significance in Autoimmune Liver Diseases
Anti-Smooth Muscle and Anti-Actin Antibodies
History
Methods of Detection, Immunofluorescence Reactivities, and Antigenic Targets
Clinical Significance
Anti-Liver Kidney Microsomal Antibody
History
Methods of Detection, Immunofluorescence Reactivities, and Antigenic Targets
Clinical Significance
Anti-Liver Cytosol Type 1 Antibody
History
Methods of Detection, Immunofluorescence Reactivities, and Antigenic Targets
Clinical Significance
Anti-Soluble Liver Antigen Antibody
History
Methods of Detection and Antigenic Targets
Clinical Significance
Anti-Neutrophil Cytoplasmic Antibody
History
Methods of Detection and Antigenic Targets
Clinical Significance
Anti-Mitochondrial Antibody
History
Methods of Detection and Antigenic Targets
Clinical Significance
Practical Points for the Clinicians
Conclusion and Future Directions
References
5: Genetics of Autoimmune Liver Diseases
Introduction
Genetics of Autoimmune Hepatitis (AIH)
HLA Variants
Non-HLA Variants
Genetics of Primary Biliary Cholangitis (PBC)
HLA Variants
Non-HLA Variants
Genetics of Primary Sclerosing Cholangitis (PSC)
HLA Variants
Non-HLA Variants
Limitations of GWASs and Future Perspectives
The Problem of Missing Heritability
The Neglected Role of X Chromosome in PBC
Epistasis (Gene–Gene Interactions)
Gene–Environment Interactions
Epigenetics: Beyond the Genes
Ancient Genetic Variants
Application of Machine Learning to Population Genetic Data
Conclusions and Open Questions
References
6: The Epigenetic Basis of Loss of Tolerance
Introduction
Tolerance and Autoimmunity
Epigenetic Mechanisms
DNA Methylation
Histone Modifications
Noncoding RNAs
Abnormal Epigenetic Modifications in Autoimmune Diseases
Dysregulated Epigenetic Modifications in SLE
DNA Hypomethylation in SLE
DNA Hypomethylation in Lupus T Cells
DNA Hypomethylation in Lupus B Cells
Histone Modifications in SLE
Noncoding RNAs in SLE
Dysregulated Noncoding RNAs in Lupus T Cells
Aberrantly Expressed MicroRNAs in Lupus B Cells
Dysregulated Epigenetic Modifications in Signaling Pathways
Environmental Factor-Induced Epigenetic Alterations in SLE
Aberrant Epigenetic Modifications in Psoriasis
DNA Methylation in Psoriasis
Dysregulated MicroRNA Mediating Modulation in Psoriasis
Abnormal Epigenetic Regulations in RA
DNA Methylation in RA
Histone Modifications in RA
Aberrantly Expressed MicroRNAs in RA
Abnormal Epigenetic Modifications in SSc
Dysregulated DNA Methylation in Systemic Sclerosis (SSc)
Dysregulated Epigenetic Modifications in T1D
DNA Methylation Status in T1D
Histone Modifications in T1D
MiRNAs in T1D
Aberrant Epigenetic Modification in PBC
DNA Methylation in PBC
Histone Modifications in PBC
MicroRNAs in PBC
Conclusion
References
7: Bile Acids and Bilirubin in Liver Immunology
Introduction
Overview of BA Homeostasis
BA Synthesis
BA Transporters and Detoxification
Cholestasis
BAs and Intestinal Microbiome
Dynamic Interplay Between BAs and the Immune Cells
BAs as Mediators Driving Hepatic Injury and Inflammation
BAs Promote Neutrophil-Driven Hepatic Immunopathology
BAs Abrogate Immunological Tolerance Induced by KCs and DCs
BAs and T lymphocytes
Impact of Immune Cells and Immune Response on BA Metabolism
Role of BA-Activated Receptors in Modulation of Liver and Gut Immunity
FXR
PXR, CAR, and VDR
BA-Activated G Protein-Coupled Receptors: TGR5, FPRs/FPRL1, and S1PR2
BAs and Their Immunomodulatory Therapeutic Potential Beyond FXR and TGR5
UDCA
NorUDCA
Other BA Metabolites
Bilirubin and Regulation of Immunity
Conclusion
References
8: The Microbiota-Gut-Liver Axis: Implications for the Pathophysiology of Liver Disease
The Gut Microbiome: An Overview
Changes in Gut Microbiota in Liver Disease
Small Intestinal Bacterial Overgrowth (SIBO)
Quantitative or Qualitative Changes in the Microbiota
Interactions with Luminal Contents: The Many Roles of Bile Acids
The Gut Barrier and the Mucosal Immune Response
The Immune Response in the Liver
Gut Microbiota and Hepatic Carcinogenesis
Future Directions
References
9: Diagnostic Liver Immunology
Introduction
Liver Biochemistries
Imaging
Assessment of Liver Fibrosis
Infectious Liver Diseases
Hepatitis A Virus
Hepatitis B Virus
Hepatitis C Virus
Hepatitis D Virus
Hepatitis E
Bacterial and Parasitic Infections
Autoimmune Liver Diseases
Primary Biliary Cholangitis
Primary Sclerosing Cholangitis
Autoimmune Hepatitis
Autoimmune Sclerosing Cholangitis
IgG4-related Sclerosing Cholangitis
Granulomatous Liver Diseases
Sarcoidosis
Common Variable Immunodeficiency
Conclusion and Future Directions
References
10: The Pathologist’s Approach to Reviewing Liver Histology
Introduction
Determination of Normal, Nonspecific Reactive, Original Liver Diseases Versus Overlapping Liver Diseases
Diagnosis of Hepatitis Versus Cholangitis
Determination of Chronic Versus Acute Liver Injury
Common Histological Findings of AIH and PBC
Necroinflammatory Changes to the Parenchyma
Portal Inflammation and Interface Hepatitis
Pathology of PBC
Appearance of Cholangitis
Appearance of CNSDC and Bile Duct Loss
Changes After Bile Duct Loss
Emergence of Hepatitic Changes
Pathology of AIH
Basic Histology
Pathological Diagnosis: Histological Components of the AIH Diagnostic Scoring System
Acute Presentation of AIH
Conclusion
References
11: Geoepidemiology of Autoimmune Liver Diseases
Introduction
Autoimmune Hepatitis
AIH in the General Population
Family Occurrence
Risk Factors
Comorbidities
Primary Biliary Cholangitis
PBC in the General Population
Family Occurrence
Risk Factors
Comorbidities
Primary Sclerosing Cholangitis
PSC in the General Population
Family Occurrence
Risk Factors
Comorbidities
Overlap Syndromes
Liver Involvement in Systemic Rheumatic Diseases
IgG4-Related Diseases
Sarcoidosis
Connective Tissue Diseases
Conclusion
References
12: Immune Responses to Bacterial Infections
Introduction
Anti-Bacterial Innate and Adaptive Immune Dysregulation in Cirrhotic Patients
Brucella
General Aspects
Immune Responses
Bartonella
General Aspects
Immune Responses
Coxiella burnetii
General Aspects
Immune Responses
Leptospira
General Aspects
Immune Responses
Listeria
General Aspects
Immune Responses
References
13: Immunity of Parasitic Infections of the Liver
Introduction
Malaria (Asymptomatic Liver Stage)
Immune Responses to Malaria Parasites
Innate Immune Responses
Adaptive Immune Responses
Schistosoma Infection
Immune Responses to Schistosoma Infection
Th1 and Th2 Cells
Regulatory T Cells
Th17 Cells
Cytokines and Cytokine Receptors
HLA Class I and Class II
IgG4 and IgE
Visceral Leishmaniasis
Immune Responses to Leishmania
The Immunobiology of Leishmaniasis
Innate Immunity
Adaptive Immunity
Conclusion
References
14: The Treatment of Bacterial and Parasitic Diseases of the Liver
Introduction
Principles in Managing Bacterial and Parasitic Diseases of the Liver
Managing Underlying CLD while Treating the Infection
Compromised Immune Response
Diminished Nutrition Status
Precautions Against Drug-Induced Liver Injury (DILI)
Bacterial Infections
Bacterial Infections in Patients with Acute Liver Failure (ALF) and Acute-on-Chronic Liver Failure (ACLF)
Common Bacterial Infections in Patients with Underlying Chronic Liver Disease
Spontaneous Bacterial Peritonitis
Urinary Tract Infection (UTI)
Pneumonia
Skin and Soft Tissue Infection (SSTI)
Bacterial Infection in Patients with  Alcoholic Liver Disease
Legionellosis
Mycobacterium Tuberculosis
Common Bacterial Infections in Patients Without Underlying CLD
Hepatic Involvement of Systemic Infection with Bacteremia: Staphylococcus aureus and Streptococcus pneumoniae
Bacterial Hepatitis: Salmonellosis
Pyogenic Liver Abscesses (PLA)
Granuloma-Related Infection: Mycobacteria
Parasitic Infections
Parasitic Infections That Commonly Occur in Patients with Underlying CLD
Giardia lamblia
Cryptosporidium
Leishmaniasis
Parasitic Infections of the Liver That Commonly Occur in Patients Without Underlying CLD
Hepatosplenic Schistosomiasis
Amebiasis
Echinococcosis
Clonorchiasis
Conclusion
References
15: Hepatitis A and Other Viral Infections
Introduction
Hepatitis A Virus
Epstein-Barr Virus
EBV Infection (Fig. 15.1)
The Role of the Immune System in EBV Infection
Role of the Immune System in EBV-Mediated Malignancy
Clinical Manifestations Affecting the Liver in Acute EBV Infection
EBV-Mediated Chronic Liver Damage
Posttransplant Lymphoproliferative Disorder
EBV-Mediated Liver Cancer
Treatment of EBV Hepatitis
Cytomegalovirus
CMV Infection and Diagnosis
The Immune Response to CMV
CMV Infection in the Immunocompetent Host
CMV Infection in the Immunocompromised Host
CMV in Liver Transplant Recipients (Fig. 15.2)
Treatment of CMV Infection
Herpes Simplex Virus
Varicella-Zoster Virus
Parvovirus (B19)
Adenoviruses
Influenza Virus
References
16: Hepatitis B Virus
Introduction
Epidemiology and HBV Genotypes
HBV Morphology and Genome Organization
HBV Viral Cycle
Host Immunity in HBV Infection: Innate Immunity
Host Immunity in HBV Infection: NK and NKT Cells
Host Immunity in HBV Infection: Adaptive Immunity
The Antiviral Mechanisms of T and B Cells
Immunomodulatory Roles of HBV Antigens
Natural History of HBV Infection
Therapy of Chronic HBV Infection
References
17: Hepatitis C
Introduction
Life Cycle of HCV: Models
Key Players in Immune Responses Against HCV
Innate Immunity Against HCV: HLA Alleles and IL-28B/IFN-λ3
Innate Immunity Against HCV: DCS, Macrophages, and NK Cells
T Cell Responses in Acute or Chronic HCV Infection
Immune Response During and After Antiviral Therapy
Anti-HCV Vaccine
Perspectives
References
18: Hepatitis D
Introduction
Epidemiology
Natural Course
HDV Diagnostic
Antiviral Therapy: PEG-Interferon and New Treatments in Development (Table 18.2)
HDV Virology
HDV and Innate Immunity
HDV and Cellular Innate Immunity
HDV and Adaptive Immunity (Table 18.3)
Conclusion
References
19: Hepatitis E
Introduction
Virology
Epidemiology
Immunopathogenesis
Innate Immune Response to HEV Infection
Adaptive Immune Response to HEV Infection
Clinical Aspects
Pregnant Women
Elderly People
Patients with Hematological Diseases
Immunosuppressed Patients
Diagnosis
Anti-HEV IgM
Anti-HEV IgG
HEV Antigen
HEV RNA
Therapy
Treatment of Acute HEV Infection
Treatment of HEV Infection in SOT Patients
Treatment of Chronic HEV Infection in Other Immunosuppressed Patients
Prevention
References
20: Alcohol-Associated Liver Disease
Introduction
Clinical Characteristics of Alcohol-Associated Liver Disease
Epidemiology and Natural History of ALD
Clinical Diagnosis of ALD
Alcoholic Hepatitis
Pathogenesis of ALD
The Effects of Alcohol, Metabolites, and Oxidative Stress
Alcohol Metabolism
Reactive Oxygen Species and Mitochondrial Stress in ALD
Endoplasmic Reticulum (ER) Stress
Decreased Antioxidants
Gut-Liver Axis in ALD
Adipose-Liver Axis in ALD
Innate and Adaptive Immune Responses
Role of Innate Immunity
Soluble Mediators
Cytokines and Chemokines
Complement
Immune Cells
Neutrophil
Kupffer Cells, Macrophages, and Monocytes
Dendritic Cells
Adaptive Immunity
Signaling Pathways
Pattern Recognition Receptors
TLRs
NOD-Like Receptors and the Inflammasome
Nuclear Receptors
MicroRNAs and EVs
Treatment for Alcohol-Associated Liver Disease
Abstinence
Current Medical Treatment
Liver Transplantation in ALD
Novel Therapeutics
References
21: Nonalcoholic Fatty Liver Disease
Introduction
Hepatic Steatosis, Insulin Resistance, and Inflammation
Oxidative Stress and Damage Pathways
Inflammatory Triggers in NASH
Innate and Adaptive Immune Cells in NAFLD and NASH
T Helper Cells
Th17 Cells
CD8 Cytotoxic T Cells
Innate T Cells
B Cells and Humoral Immunity
Myeloid Cells
Therapeutic Implications
Conclusion
References
22: Primary Biliary Cholangitis
Introduction
Historical Background
Pathogenesis
Autoimmune Responses Against Mitochondrial Antigens
Interaction of BECs and Autoimmunity
Genetic Predisposition
Environmental Triggering Factors
Epidemiology
Diagnosis
Liver Enzymes: Consistent Elevation of Cholestatic Enzymes
Serological Tests: Detection of AMA
Liver Histology: CNSDC
Atypical Cases
AMA-Negative PBC
PBC with AIH Features (PBC/AIH Overlap)
Treatment
UDCA
Obeticholic Acid
Fibrates and Other PPAR Agonists
LT
Management of Symptoms and Extrahepatic Manifestations
Fatigue
Pruritus
Disorders Associated with PBC
Sicca Syndrome
Osteopenia and Osteoporosis
Hyperlipidemia and Metabolic Syndrome
Hepatocellular Carcinoma
Stratification of the Risk for Progression
Stratification at Baseline
Stratification During Treatment
Future Perspective
References
23: PSC-AIH Overlap
Case Presentation and Introduction
Overview of PSC Characteristics
Overview of AIH Characteristics
Patients with Overlapping Features Between PSC and AIH
Definitions and Terminology Issues
Pathogenesis
PSC-AIH Variant
Epidemiology and Diagnosis
Treatment and Outcome
Autoimmune Sclerosing Cholangitis (ASC)
Epidemiology and Diagnosis
Treatment and Outcome
Management of Other Complications
Conclusion
References
24: Primary Biliary Cholangitis: Autoimmune Hepatitis Overlap Syndrome
Introduction
Clinical Presentation of Overlap Syndrome
Diagnosis of Overlap Syndrome
Diagnostic Criteria
Biochemical Features
Serology
Liver Biopsy
Course of the Disease and Therapy
Other Therapies
Associated Extra-hepatic Autoimmune Diseases
PBC-PSC Overlap Syndrome
Conclusion
References
25: Primary Sclerosing Cholangitis
Introduction
Epidemiology
Natural History
Clinical Features
Imaging Findings
Histology
Etiology and Pathogenesis
Genetic Factors
Diagnosis
PSC and IBD
Immune Responses
Lymphocyte Trafficking
PSC Dysbiosis
Toxic Bile Theory
Biliary Epithelial Cells
Infectious and Antigenic Factors
Treatment
Medical Treatment of Underlying Disease
Endoscopic Management
Percutaneous Management
Biliary Surgery
Liver Transplantation
References
26: Autoimmune Hepatitis
Introduction
Epidemiology
Aetiology and Pathogenesis
Genetics
Potential Triggers
Mechanisms of Liver Damage
Loss of Self-Tolerance
Animal Models
Clinical Presentation and Natural History
Diagnosis and Scoring Systems
Laboratory
Autoantibodies
Anti-Nuclear Antibodies
Anti-Smooth Muscle Antibodies
Anti-Liver-Kidney-Microsomal Type 1 Antibodies
Anti-Liver Cytosol Type 1 Antibodies
Anti-Soluble Liver Antigen/Liver-Pancreas Antibodies
Anti-Neutrophil Cytoplasmic Antibodies
Anti-Asialoglycoprotein Receptor Antibodies
Histology
Treatment
Standard Treatment
Alternative and New Treatments
6-Mecaptopurine
Mycophenolate Mofetil
Cyclosporine/Tacrolimus
Infliximab
Rituximab
Liver Transplantation
Special Presentations
Variant Syndromes
Acute Severe to Fulminant AIH
AIH and Pregnancy
References
27: IgG4-Related Disease: Current Concept, Diagnosis, and Pathogenesis
Introduction
Current Concepts of IgG4-RD
Diagnosis of IgG4-Related Disease
Clinical Examination
Laboratory Examination
Histopathologic Examination
Current Concept and Diagnosis OF IgG4-SC
Bile Duct Images of IgG4-SC
Cholangiogram
Circular/Symmetric Thickening of the Bile Duct
Characteristic Hematological Findings
Histopathological Findings of Bile Ducts
Diagnosis of IgG4-SC Using the Japanese Clinical Diagnostic Criteria
Current Concept of IgG4-Related Hepatopathy and IgG4-Related Autoimmune Hepatitis
Recent Advances in the Pathogenesis of IgG4-RD
Immunogenetic Backgrounds
Innate Immunity
Possible Roles of IgG4 in IgG4-RD
The Complement System
Autoantibodies and Candidate of Target Antigens
Role of B Cells
Th1 and Th2 Immune Balance
Regulatory T Cells
Conclusion
References
28: Pediatric Liver Disease
Biliary Atresia
Alagille Syndrome
Progressive Familial Intrahepatic Cholestasis (PFIC)
Alpha-1 Antitrypsin Deficiency
Nonalcoholic Fatty Liver Disease (NAFLD)
Epidemiology
Screening and Diagnosis
Management
Viral Hepatitis
Hepatitis B
Management
Hepatitis C
Management
Acute Liver Failure (ALF)
Diagnostic Approach
Management
Liver Transplant in the Setting of ALF
Prognosis
Metabolic Liver Disorders
Glycogen Storage Disorders (GSD)
GSD I
GSD Ib
GSD II (Pompe Disease)
GSD III
GSD IV
GSD VI
GSD IX
GSD XI (Fanconi- Bickel Syndrome)
Mitochondrial Respiratory Chain Disorders
Urea Cycle Disorders
Fatty Acid Oxidation Disorders (FAO Disorders)
Wilson Disease
Autoimmune Liver Disease
Recurrent Autoimmune Hepatitis and De Novo Autoimmune Hepatitis
Sclerosing Cholangitis
References
29: Mechanisms of Acute Liver Failure
Introduction
Mechanisms of Disease
Etiology
Infectious Causes
Hepatitis A Virus
Hepatitis B Virus
Hepatitis C Virus
Hepatitis E Virus
Rare Cases of Viral Hepatitis
Drugs, Toxins, Chemicals
Acetaminophen
Mushroom (Amanita) Poisoning
Halothane
Cardiovascular Disorders
Budd-Chiari Syndrome
Metabolic Disorders
Wilson’s Disease
Mechanisms of Organ Failure
Encephalopathy and Cerebral Edema
Cardiovascular Dysfunction
Infection
Pulmonary Complications
Renal Failure
Metabolic Complications
Coagulation Disorders
Pathophysiological Aspects of ALF
Dysregulation of the Cytokine Network in ALF
IL-6/gp130-Dependent Signals
TNF-Dependent Pathways
Endotoxin/Galactosamine Model
Galactosamine/TNF Model
Concanavalin A Model
Apoptosis and Necrosis in ALF
Cytokeratin-18 as a Prognostic Biomarker in ALF
Intestinal Microbiome and Acute Liver Failure
Translation of Experimental Data Into Therapeutic Approaches in Humans
Concluding Remarks and Open Questions
References
30: Immune-Mediated Drug-Induced Liver Injury
Introduction
Immunoallergic DILI: Signs of Hypersensitivity
Immune Mechanisms Underlying the Pathogenesis
Generation of Hapten
Role of Adaptive Immune System
Loss of Immune Tolerance
Danger Signals
Innate Immune System
Histology in Immunoallergic Hepatitis and Other Types of DILI
Drug-Induced Autoimmune Hepatitis (DIAIH)
Risk Factors for Drug-Induced Autoimmune Hepatitis
The Role of Specific Drugs
Nitrofurantoin
Minocycline
Statins
Anti-Tumor Necrosis Factor α (TNF α) Agents
Checkpoint Inhibitors
Diagnosis
Therapy
Conclusion
References
31: Hepatobiliary Cancers and Immunology
Introduction
Epidemiology
Molecular Pathogenesis and Classification
Diagnosis and Treatment
Overview of Cancer Immunology
Cytotoxic T Cells
Treg Cells
NK Cells
NKT Cells
Macrophages
MDSCs
B cells
HCC Immunology
Cytotoxic T Cells
Tregs
NK Cells
NKT Cells
B cells
DC Cells
Macrophages (TAMs, Kupffer Cells)
MDSCs
HCC Genetic Drivers and Immune Regulation
Immunotherapy of HCC
Checkpoint Inhibitors
Cancer Vaccines and DC-Based Immunotherapy
NK Cells-Based Immunotherapy
Cytokine-Induced Killer (CIK) Cell-Based Immunotherapy
Target MDSCs
Target TAMs
Target Treg Cells
TCR-Engineered T-cell-Based Immunotherapy
CAR-Engineered T-cell Immunotherapy
Conclusion
References
32: Acute-on-Chronic Liver Failure
Defining Acute-on-Chronic Liver Failure
Concept of Functional Reserve or Critical Mass
Differentiating ACLF From Acute Decompensation
What Constitutes an Acute Insult?
Etiology and Pathogenesis of the Acute Insult
Alcohol-Related ACLF
Hepatitis B Infection
Acute Viral Hepatitis
Drug-Induced Liver Injury
Sepsis and ACLF
Acute Variceal Bleed
Autoimmune Hepatitis
Other Insults
Defining the Chronic Etiology
Pathophysiology of ACLF
Inflammation
Immunological Basis of ACLF
Role of Histology in Predicting Outcome in ACLF
Disease Prognostication and Scoring Models
Management of ACLF and Organ Failures
Need for ICU Care
Concept of Organ Failure and Dysfunction
Specific Treatment
Alcoholic Hepatitis
HBV Treatment
Autoimmune Hepatitis
Liver Support Devices
Liver Transplantation in ACLF
Newer Therapeutics in ACLF
Prevention of ACLF
Conclusion
References
33: The Pathogenesis of Liver Diseases in Pregnancy
Introduction
Physiologic Changes in the Liver During Pregnancy
Liver Diseases Unique to Pregnancy
Acute Fatty Liver of Pregnancy
Pathogenesis
HELLP Syndrome
Criteria for the Diagnosis of HELLP Syndrome
Histology in HELLP Syndrome
Pathogenesis of HELLP
Hyperemesis Gravidarum
Pathogenesis of Hyperemesis Gravidarum
Intrahepatic Cholestasis of Pregnancy
Pathogenesis of Intrahepatic Cholestasis of Pregnancy
Preeclamptic Liver Dysfunction (Preeclampsia with Severe Features)
Pathogenesis of Preeclampsia
Liver Diseases Not Unique to Pregnancy
Neonatal Lupus
Pathogenesis of Neonatal Lupus
Patients with Preexisting Liver Disease
Autoimmune Hepatitis and Pregnancy
Pathogenesis of Autoimmune Hepatitis
Conclusion
References
34: Graft-Versus-Host Disease
Introduction
Engraftment After Hematopoietic Cell Transplantation
Overview
Composition of Donor Grafts
Recovery of Immune Functions in the Host
Recovery of Innate Immunity
Recovery of Adaptive Immunity
Cellular Immunity
Humoral Immunity
Factors Affecting Host Immune Reconstitution
Biomarkers of Host Immune Reconstitution
Graft-Versus-Host Reaction and Graft-Versus-Host Disease
Graft-Versus-Tumor and Graft-Versus-Leukemia Responses
Standardized Definitions for Acute and Chronic GVHD
Epidemiology of Acute and Chronic GVHD
Acute GVHD
Chronic GVHD
Risk Factors for Acute and Chronic GVHD
Clinical Features, Diagnosis, Grading, Therapy, and Prognosis of Acute and Chronic GVHD
Prophylaxis to Prevent Acute GVHD
Acute GVHD
Diagnostic Criteria for Acute GVHD
Target Organs in Acute GVHD
Organ-Specific Manifestations of Acute GVHD
Skin
Intestine
Liver
Grading of Severity in Acute GVHD
Biomarkers for Acute GVHD
Treatment of Acute GVHD
Prognosis of Patient with Acute GVHD
Chronic GVHD
Diagnostic Criteria for Chronic GVHD
Target Organs in Chronic GVHD
Organ-Specific Manifestations of Chronic GVHD
Skin
Intestine
Liver
Eye
Mouth and Oropharynx
Lung
Female and Male Genital Tract
Musculoskeletal System
Hematopoietic System
Immunologic System
Grading of Severity in Chronic GVHD
Biomarkers for Chronic GVHD
Treatment of Chronic GVHD
Prognosis of Patient with Chronic GVHD
GVHD After Solid Organ Transplantation
Overview
Incidence
Clinical Features
Treatment and Prognosis
Pathogenesis of Acute and Chronic GVHD
Overview
Genetic Factors in HCT
Role of HLA Matching
Minor Histocompatibility Antigens
Non-HLA Genes
Cytokine Genes
Microbiome and Disruption of Intestinal Functions
Pathogenesis of Acute GVHD
Step 1: Systemic Priming Effects of Conditioning Chemotherapy and Radiation
Step 2: Activation of Host Antigen-Presenting Cells
Step 3: Alloactivation and Costimulation of Donor T Cells
Step 4: Donor Effector Cell Injury of Host Tissues
Step 5: Perpetuation of Donor-Mediated Destruction of Host Tissues
Pathogenesis of Chronic GVHD
Three-Phase Model of Chronic GVHD Pathogenesis
Phase 1: Control of Initial Inflammation and Tissue Injury After HCT
Phase 3: Chronic Fibrosis, Tissue Injury, and Failure of Tissue Repair
GVHD Predilection for the Skin, Intestine, and Liver
Future Directions
Prevention of the Need for HCT
Improvement in the Success of HCT
Development of Therapies for Acute and Chronic GVHD with Greater Safety and Efficacy
References
35: Immunopathogenesis of Liver Cirrhosis
What Is Liver Fibrosis, and How Does It Evolve to Liver Cirrhosis?
HSCs Sense Changes in Their Microenvironment Under Inflammatory Conditions
Danger-Associated Molecular Patterns (DAMPs) (Such as High-Mobility Group Protein 1 [HMG-1], Mitochondrial DNA [mtDNA])
Pathogen-Associated Molecular Patterns (PAMPs) (Such as Bacterial Products)
Other Inflammatory Mediators (Such as Apoptotic Bodies, Extracellular Vesicles)
Cytokines Regulate Liver Fibrosis Initiation, Progression, or Resolution
Major Cytokines That Promote Liver Fibrosis
Major Cytokines That Attenuate Liver Fibrosis
Other Cytokines That May Have Dual Roles in the Control of Liver Fibrosis
Immune Cells Regulate Liver Fibrogenesis
Liver-Resident Macrophages
Monocyte-Derived Macrophages
Neutrophils
Natural Killer (NK) and NKT Cells
T Lymphocytes
B Lymphocytes
Mucosal-Associated Invariant T (MAIT) Cells
Roles of Immune Cells in Fibrosis Resolution
Potential Anti-fibrotic Therapeutic Approaches by Targeting Immune Components
References
36: Immune-Mediated Liver Disease in the Transplanted Liver
Introduction
Ischemia–Reperfusion Injury (IRI)
Molecular Mechanisms of Ischemia–Reperfusion Injury
Altered Redox Status and Reduced Microcirculatory Blood Flow
Ionic and Mitochondrial Disturbances
Cellular Cascade
Potential Therapeutic Targets for IRI
Allograft Rejection
Immunobiology of Rejection
Clinicopathological Features
Acute Antibody-Mediated Rejection (AMR)
ABO-Compatible Allografts
Treatment Considerations
Chronic Antibody-Mediated Rejection (AMR)
Acute T-Cell-Mediated Rejection (TCMR)
Molecular Mechanisms of Acute TCMR
Pathological Findings
Treatment Considerations and Outcome
Chronic T-Cell-Mediated Rejection
Molecular Mechanisms
Pathological Findings
Treatment Considerations
Graft Hepatitis
The Liver as a Tolerogenic Allograft
Microchimerism
Potential Barriers to Developing Tolerance
Donor–Recipient HLA Matching
Memory T-Cell Responses
Infection
Operational Tolerance Following Transplantation [65]
Clinical Experiences of Immunosuppressive Withdrawal Following Liver Transplantation
Applied Immunology and Future Prospects
Novel and Ongoing Therapeutic Approaches to Promote Liver Transplant Tolerance
Recurrent Autoimmune Disease Following Transplantation (Table 36.3)
Recurrent Primary Biliary Cholangitis (PBC)
Etiopathogenesis and Molecular Mechanisms
Treatment Considerations and Outcome
Recurrent Primary Sclerosing Cholangitis (PSC)
Etiopathogenesis and Molecular Mechanisms
Treatment Considerations and Outcome
Recurrent Autoimmune Hepatitis (AIH)
Etiopathogenesis and Molecular Mechanisms
Treatment Considerations and Outcome
Plasma Cell Hepatitis: De Novo Autoimmune Hepatitis
Conclusion
References
Index